Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glycolytic enzymes are known to play pivotal roles in cancer cell survival, yet their molecular mechanisms remain poorly understood.
Phosphoglycerate mutase 1
(
PGAM1
) is an important glycolytic enzyme that coordinates glycolysis, pentose phosphate pathway, and serine biosynthesis in cancer cells. Herein, we report that
PGAM1
is required for homologous recombination (HR) repair of DNA double-strand breaks (DSBs) caused by DNA-damaging agents. Mechanistically,
PGAM1
facilitates DSB end resection by regulating the stability of CTBP-interacting protein (CtIP). Knockdown of
PGAM1
in cancer cells accelerates CtIP degradation through deprivation of the intracellular deoxyribonucleotide triphosphate pool and associated activation of the p53/p73 pathway. Enzymatic inhibition of
PGAM1
decreases CtIP protein levels, impairs HR repair, and hence sensitizes BRCA1/2-proficient breast cancer to poly(ADP-ribose) polymerase (
PARP
) inhibitors. Together, this study identifies a metabolically dependent function of
PGAM1
in promoting HR repair and reveals a potential therapeutic opportunity for
PGAM1
inhibitors in combination with
PARP
inhibitors.
...
PMID:Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells. 2873 77
